November 14, 2023
We appreciate the opportunity to comment and support the Food and Drug Administration (FDA) proposed rule regarding: “Medical Devices With Indications Associated With Weight Loss Guidances; Draft Guidances for Industry and Food and Drug Administration Staff.”
The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
The issue of medical devices being used for weight-loss, weight-management, and associated comorbidities is an important one to address as the landscape of medical devices innovation changes. It is essential that future guidance issued by the FDA is unbiased, based on sound science, and prioritizes the health and safety of patients.
We recommend the following changes to improve the Medical Devices with Indications Associated with Weight Loss – Clinical Study and Benefit-Risk Considerations draft guidance:
- Diversity in study samples
We agree with the view that study populations should accurately reflect the diversity of the relevant clinical populations. However, lines 276-278 states, “We recommend that submitters include in their study a representative sample of patients from various demographic groups (e.g., sex, gender, age, ethnic, and racial) in which the prevalence of obesity is highest.” We disagree. All demographic groups should be included, and in large enough numbers to conduct subgroup analyses to determine safety and effectiveness for people in that demographic group. It is not enough to include different demographic subgroups; the numbers must be large enough to provide meaningful data.
- Use and Management of Sham Devices
Page 5, lines 196-208 discusses the utility of sham devices as a control to study the intended devices’ effectiveness compared to placebo, sham studies play a pivotal role in accurately evaluating the benefits of intended interventions, since it has been established that even sham surgery can have a positive “placebo” effect.
However, the FDA should specify explicit safety guidelines for sham control groups. Considerations such as the method of insertion, the longevity of these devices, and their post-implant upkeep are crucial factors that warrant explicit attention in order to ensure the ethics and safety of studies involving sham devices.
- Study Duration and Follow-up
We concur with the FDA that benchmarks for different time durations post-intervention should be established in the proposed clinical trial design. On page 6, lines 220-221, it states, “For a proposed indication of “weight loss,” the duration of device use and primary endpoint should typically demonstrate weight loss at 12 months or more.” We agree that 12 months should be the minimum follow-up, and FDA should specify what would qualify as “long-term weight loss.” We suggest 2 years, 3 years, and 5 years.
This guidance should more clearly specify appropriate metrics for “durability of weight loss.” The durability of the weight loss obtained should be considered a critical metric for the success or failure of interventions, and FDA should specify how to define long-term follow-up.
- Behavioral and Psychiatric Implications
Table 4 on page 20 discusses “factors considered as part of the benefit-risk evaluation for devices with indications associated with weight loss.” Many factors are considered, but behavioral, psychological, or psychiatric changes associated with such medical devices are not explicitly addressed in this guidance. For example, a benefit could be quantified in terms of a decrease in symptoms of depression and social anxiety. In contrast, if the medical device leads to adverse events that interfere with daily activities or self-esteem, that needs to be evaluated.
In summary, it is essential to precisely define the intended impact of these devices on participants’ weight but also on other traits that affect health and quality of life. For that reason, these devices should be comprehensively studied on diverse populations with long-term follow-up and stringent controls. Adhering to these principles will pave the way for devices that are safe and effective for the types of patients for whom they are approved.